Heart failure-the experience of living with end-stage heart failure and accessing care across settings.

BACKGROUND: Heart failure is a complex clinical syndrome affecting an increasing number of the ageing population. Patients and carers require increasing input from specialist palliative care services to both manage symptoms and access support in the last year of life. An integrated clinical service between the local cardiology team at Princess Royal University Hospital and the palliative care team at St. Christopher's Hospice was piloted for patients with end-stage heart failure in Bromley in Kent, UK. This study explored views of patients and carers who participated in the integrated pilot service. METHODS: A qualitative study was conducted in which a convenience sample of patients and carers were invited to participate in focus groups: two bereaved carer groups (n=2, n=2); one patient group (n=4), held between 14th December 2018 and 18th January 2019. Participants were asked to describe their experiences of care received facilitated by a topic guide. Interviews were recorded, transcribed and coded using thematic analysis to identify common themes. RESULTS: Four patients (2:2 M:F) aged between 70 to 87 years and four female carers whom had cared for patients aged between 70 to 96 years who were since deceased, participated in this study. Overall, the service was positively received, and responses were mapped into four key areas; being diagnosed and living with heart failure, referral to palliative care, key helpful components of the care received and finally, unhelpful components of the new service in terms of care. Common themes emerged including understanding of heart failure and its trajectory, communication around palliative care, having a 'broker' for the system, recognition of carer's needs, service responsiveness, and feeling 'in control'. CONCLUSIONS: This qualitative study highlighted important considerations when developing an integrated heart failure and palliative care service. Education about heart failure for patients and carers, but also the integrated multidisciplinary team is crucial to improving detection of deterioration and facilitating communication around Advance Care Planning. The value of the 'expert-carer' should also be promoted and supported in chronic conditions. We recommend a focus on development of integrated services that enable joined-up care or single point of contact for patients and carers.

Does palliative chemotherapy really palliate and are we measuring it correctly? A mixed methods longitudinal study of health related quality of life in advanced soft tissue sarcoma.

OBJECTIVE: Soft tissue sarcoma (STS) is a rare cancer type that when locally advanced or metastatic, is predominantly treated with palliative chemotherapy with the aim of improving both quantity and quality of life. Given modest survival data after commencing first line chemotherapy, this study examines (i) what constitutes health related quality of life (HRQoL), (ii) whether the most commonly used HRQoL assessment tool measures this and (iii) to what extent HRQoL, and its components, change during and after treatment. DESIGN: Mixed-methods longitudinal study of 66 sarcoma patients living with STS (42 commencing chemotherapy, 24 under surveillance after completing chemotherapy) involving serial EORTC QLQ-C30 questionnaires and nested-qualitative semi-structured interviews with a sub-sample of participants. EORTC QLQ-C30 score change from baseline to primary evaluation point was examined using a paired t-test. Interviews were analysed using the framework approach before both datasets were integrated. RESULTS: Five main factors, including control of pain, were identified by study participants as important components of HRQoL; these are examined within the EORTC QLQ-C30. However, others e.g. independence loss and common causes of anxiety, are not. Whilst social and psychological domains are addressed by the EORTC QLQ-C30, the quantitative change over time did reflect qualitative descriptions of decline. The mean overall EORTC QLQ-C30 HRQoL score deteriorated from baseline (60.4) to the primary evaluation point (50.2) [change of -10.2, t-test: -2.70, p = 0.01] for those receiving chemotherapy; this was in concordance with patients' qualitative accounts. Baseline overall HRQoL scores were higher in the surveillance group suggesting a correlation with chemotherapy response and longer-term improvement in HRQoL. The evidence from both HRQoL scores and qualitative accounts indicated that the presence and control of physical symptoms were particularly important in maintaining HRQoL. Whilst fatigue deteriorated on chemotherapy (baseline 41.7 to 52.8; change of +11.1, t-test +2.51, p<0.05), pain (baseline 41.5 to 32.1; change -9.4, t-test -2.06 p<0.05) and sleep disturbance (43.1 to 28.5; change -14.6, t-test -3.05, p<0.05) both improved. CONCLUSION: A key finding was that the EORTC QLQ-C30 assesses some but not all of the patient-reported components of HRQoL in sarcoma patients highlighting the need for either STS specific modules within the EORTC QLQ-C30 or a completely new STS specific HRQoL tool. First line palliative chemotherapy improves specific symptoms known to be prevalent and to influence HRQoL in this patient group which in some patients may translate to sustained improvement in HRQoL: further exploration and validation of these findings in larger prospective studies are warranted.

'When something is this rare how do you know bad really is bad ?'-views on prognostic discussions from patients with advanced soft tissue sarcoma.

OBJECTIVES: Prognostic disclosure among patients with cancer permits open informed discussion about treatment preferences and encourages advance care planning. In rare cancers such as soft tissue sarcoma, discussions regarding prognostication are challenging. Little is known about the consequences of this for patients or their preferences for such information. This qualitative study explores patient-centered accounts of the value and timing of prognostic discussions. METHODS: 24 semistructured interviews were conducted with soft tissue sarcoma patients attending one London cancer centre: 66% female, median age 53 (range 19-82). The study was cross-sectional and participants were at different stages of the advanced disease trajectory. Interviews were digitally recorded, transcribed verbatim and analysed thematically using the framework approach. RESULTS: All participants understood the incurable nature of advanced sarcoma. However, prognostic discussions were rare, always patient initiated and did not include known survival data, despite direct participant enquiry. Most participants did not wish to discuss prognosis at initial diagnosis but wished to be offered the opportunity to discuss this at intervals of disease progression, despite reservations it may not be helpful. Participants expected discussions to be clinician initiated. Three themes emerged to explain this position and included (1) Rarity causing prognostic uncertainty referring to patient belief that prognostication in rare cancers was less likely to be accurate than for common tumours; (2) Avoiding the negatives referring to a wish not to hear unfavourable information and (3) Physical symptoms a better prognostic indicator than 'physician guess'. CONCLUSIONS: Although 17/24 participants preferred not to discuss prognosis at initial diagnosis, they wished to have the opportunity to revisit prognostic discussions at intervals of disease progression. This may facilitate better advance care planning and end of life care.

Symptom Burden in Advanced Soft-Tissue Sarcoma.

CONTEXT: There is little information on symptom prevalence and severity in advanced soft-tissue sarcoma (STS). Understanding symptom burden will aid clinical consultations, clarify which symptom interventions are needed, and better define optimum timings of palliative and supportive care referrals. OBJECTIVES: To describe symptom prevalence and severity in patients undergoing different treatment options for advanced STS: 1) first-line palliative chemotherapy (FLC), 2) active surveillance (AS) pre- and post-FLC, and 3) palliative care (PC) alone. METHODS: Cross-sectional survey in one sarcoma center using the patient-reported Memorial Symptom Assessment Scale-Short Form (MSAS-SF). Symptom prevalence, severity, and MSAS-SF subscales were recorded before commencing a new treatment. Our results were compared with other MSAS-SF cancer and noncancer data. RESULTS: One-hundred and thirteen patients (mean age, 59 years) were recruited. Forty-two commenced FLC, 27 started AS pre-FLC, 24 AS post-FLC, and 20 PC alone. Median overall number of reported symptoms was 11 (range 1-31): which when stratified by treatment meant AS pre-FLC < AS post-FLC < FLC < PC alone (most symptomatic). The commonest physical symptoms were pain (77%; 95% CI 68-84), lack of energy (73%; CI 63-81) difficulty sleeping (56%; CI 46-65), feeling bloated (49%; CI 39-58), and dyspnea (49%; CI 39-58). Distress levels were commensurated with prevalence except for dyspnea, which was disproportionally less distressing. Psychological distress was moderate (mean MSAS-PSYCH: 1.39) but higher than comparative cancer data. CONCLUSION: Advanced STS patients have a clinically important symptom burden comparable to other cancers. Common symptoms should be screened and addressed appropriately, including timely PC involvement.

Towards a pain free hospital: an in-depth qualitative analysis of the pain experiences of head and neck cancer patients undergoing radiotherapy.

BACKGROUND: Treatment for head and neck cancer can frequently be a painful experience with implications for patients in terms of quality of life, nutrition and ultimately treatment outcomes. Pain may arise for a number of reasons in this patient group including the influence of localised tissue damage from radiotherapy, the effects of chemotherapeutic agents as well as the disease process itself. Early identification of cancer pain, through screening and early analgesic and pain management are thought to be the most appropriate approaches to the problem. AIM: To explore in-depth, patients' views of the experience of pain related to radiotherapy for head and neck cancer, within the context of a randomised controlled trial (RCT) of pain screening and intervention. SAMPLE: A purposive sample of head and neck cancer patients undergoing radiotherapy who were participating in a separate RCT of a proactive pain screening intervention. METHODS: A qualitative design using one-off, face-to-face, in-depth interviews. Data were inductively analysed for themes using thematic analysis. Data were collected from September 2012 to January 2013. FINDINGS: Eight participants were interviewed. Several issues around pain management arose and the influence of various factors became apparent. Four dominant themes emerged: facets of radiotherapy pain in head and neck cancer, facilitators and barriers to pain management, pain services and finally interdisciplinary working. CONCLUSION: The specific issues faced by head and neck cancer patients undergoing radiotherapy highlight the need for pain relieving interventions delivered by pain specialists, in tandem with the development of robust self-management strategies. An integrated approach to care is optimal, comprising pain screening at each outpatient encounter, and review by specialists as necessary.

Modelling the PKPD of oxycodone in experimental pain - Impact of opioid receptor polymorphisms.

BACKGROUND: Polymorphisms in the opioid receptor genes may affect the pharmacodynamics (PD) of oxycodone and be part of the reason behind the diversity in clinical response. The aim of the analysis was to model the exposure-response profile of oxycodone for three different pain variables and search for genetic covariates. Model simulations were used to predict how population and effect-size impact the power to detect clinical significant SNPs. METHOD: The population pharmacokinetic-pharmacodynamic (PKPD) model of oral single-dosed oxycodone was based on pooled data from three published studies in healthy volunteers. Pain tolerance data from muscle pressure (n=36), visceral pressure (n=54) and skin pinch (n=34) were included. Genetic associations with 18 opioid-receptor SNPs were explored using a stepwise covariate approach. Model simulations were performed using the estimated model parameters. RESULTS: None of the selected SNPs were associated with analgesic response of oxycodone at P<0.001. Baseline response in muscle cuff pressure was associated with OPRK1 rs7016778 and rs7824175 (P<0.001). Simulations indicated that large differences in drug response between genotypes (>50% for similar population sizes) or large populations (n>200 for a 20% response difference) are necessary to identify clinical significant SNP effects due to high population variability. CONCLUSION: A population PKPD model has been developed for oral oxycodone using three different pain variables to explore impact of genetic covariates and study design. None of the selected polymorphisms were significantly associated with analgesic response of oxycodone, but an association of baseline response in muscle cuff pressure with two OPRK1 SNPs was identified.

Palliative care for patients with advanced fibrotic lung disease: a randomised controlled phase II and feasibility trial of a community case conference intervention.

BACKGROUND: Those affected by advanced fibrotic interstitial lung diseases (ILDs) have considerable unmet symptom and psychological needs. Case conferencing has been proposed to address these issues, but requires evaluation. AIM: To obtain preliminary information on the impact of a case conference intervention delivered in the home (Hospital2Home) on palliative care concerns of patients and their carers, and to evaluate feasibility and acceptability. METHODS: Hospital2Home was trialled at a specialist centre using a Phase II fast-track randomised controlled trial with qualitative interviews. The primary outcome for effect was mean change from baseline of Palliative Care Outcome Scale (POS) (a measure of symptoms and concerns) at 4 weeks. Secondary outcomes included symptom control, quality of life, consent and recruitment rates and percentage of patients in the fast-track group receiving case conferences within 14 days. RESULTS: 53 patients were recruited (26 fast-track, 27 controls). Mean (SD) POS scores at 4 weeks were -5.7 (7.5) fast-track vs -0.4 (8.0) control, (mean change difference between the two arms was -5.3 (95% CI -9.8 to -0.7) independent t test p=0.02); effect size (95% CI) -0.7 (-1.2 to -0.1). The secondary outcomes of quality of life, anxiety and depression were superior in the fast-track arm, and none were worse. Qualitative findings corroborate these data. Recruitment was successful and 53/67 (79%) of eligible patients consented. 6/25 (24%) had case conferences within 14 days. CONCLUSIONS: Community case conferences improve palliative symptoms and quality of life after 4 weeks. Hospital2Home for the most part is both feasible and acceptable. It now requires further testing in multicentre trials. TRIAL REGISTRATION NUMBER: NCT01450644.

The palliative care needs for fibrotic interstitial lung disease: a qualitative study of patients, informal caregivers and health professionals.

BACKGROUND: While there have been some studies looking at the impact on quality of life of patients with idiopathic pulmonary fibrosis, to date no qualitative research looking at the specialist palliative needs of these patients has been conducted. AIM: This study aims to explore the specialist palliative care needs of people living with end-stage progressive idiopathic fibrotic interstitial lung disease. DESIGN AND SETTINGS/PARTICIPANTS: In total, 18 qualitative semi-structured in-depth interviews were conducted with patients, their informal caregivers and health professionals across two specialist interstitial lung disease centres in London and in the community. RESULTS: Many participants reported uncontrolled symptoms of shortness of breath, cough and insomnia, which profoundly impacted every part of patients' and informal caregivers' lives. Psychologically, patients were frustrated and angry at the way in which their illness severely limited their ability to engage in activities of daily living and compromised their independence. Furthermore, both patients and informal caregivers also reported that the disease seriously affected family relationships where strain was pronounced. There was varied knowledge and confidence among health professionals in managing symptoms, and psychosocial needs were often underestimated. CONCLUSION: This study is the first of its kind to examine in depth the impact of symptoms and psychosocial needs revealing the profound effect on every aspect of progressive idiopathic fibrotic interstitial lung disease patients' and informal caregivers' lives. Education and guidance of appropriate palliative care interventions to improve symptom control are needed. A case conference intervention with individualised care plans may help in addressing the substantial symptom control and psychosocial needs of these patients and informal caregivers.

Palliative care for people with non-malignant lung disease: summary of current evidence and future direction.

BACKGROUND: The physical and psychosocial needs of patients with chronic non-malignant lung disease are comparable to those with lung cancer. This article will focus on chronic obstructive pulmonary disease, interstitial lung disease and cystic fibrosis as examples of life-limiting, non-curable and non-malignant lung diseases. THE NEED FOR SUPPORTIVE AND PALLIATIVE CARE: Recent national guidance has demanded that palliative care is inclusive of all patients with life-limiting disease, irrespective of diagnosis, and that specialist palliative care teams are involved in the management of patients on a basis of need rather than prognosis. WHAT IS KNOWN: Despite medical therapy, most patients with moderate to severe chronic obstructive pulmonary disease, interstitial lung disease and cystic fibrosis experience pain, fatigue and dyspnoea, with the majority not getting relief from dyspnoea towards the end of life. Furthermore, dyspnoea causes social isolation and difficulty performing activities of daily living and impairs quality of life. There is an increasing evidence base for the assessment of supportive and palliative care needs, symptom interventions, prognostication, models of service delivery and implications of these for clinical practice and research in non-malignant lung diseases. WHAT IS UNKNOWN: Despite advances, much still remains unknown regarding assessment, management and prognostication in individual chronic non-malignant lung diseases. Although different service models are being used in clinical practice, the optimal model(s) of service delivery remain unknown. IMPLICATION FOR FUTURE RESEARCH, POLICY AND PRACTICE: We describe key areas for further research, which include the need for large, high-quality trials of pharmacological and non-pharmacological interventions and their combinations as well as evaluation of the efficacy and cost-effectiveness of models of care. As access to palliative care is poor for these patients, the barriers to referral need to be understood and reduced, which along with effective working between palliative care teams, with respiratory services backup, should optimise delivery of care in patients with life-limiting non-malignant lung disease.

Plasma morphine and metabolite concentrations are associated with clinical effects of morphine in cancer patients.

CONTEXT: Morphine is the opioid of choice for cancer-related pain, but for many patients the benefits of morphine are outweighed by its side effect profile. Morphine is metabolized to morphine-3-glucuronide and morphine-6-glucuronide; however, little is known about the contribution of these metabolites to analgesia and morphine-related side effects. OBJECTIVES: We investigated the association between plasma morphine and metabolite concentrations and the clinical effects of morphine in cancer patients. METHODS: A prospective study was performed in cancer patients taking oral morphine for moderate-to-severe cancer pain. Subjects who responded well to morphine (responders) and subjects who failed to respond to morphine because of lack of analgesia and/or the presence of intolerable side effects (nonresponders/switchers) were recruited. Pain and toxicity scores were recorded and blood samples were analyzed for plasma morphine, morphine-3-glucuronide, and morphine-6-glucuronide concentrations. RESULTS: Results showed that 1) morphine responders have higher plasma morphine and metabolite concentrations compared with nonresponders, 2) lower pain scores are associated with higher plasma morphine and metabolite concentrations, 3) central side effects are associated with a higher metabolite:plasma morphine ratio, and 4) myoclonus is associated with extremely high concentrations of plasma morphine and metabolites. CONCLUSION: This study has shown that plasma morphine and metabolite concentrations are associated with the clinical effects of morphine therapy. These results are important because they demonstrate the relevance of measuring plasma metabolite concentrations in clinical trials and the potential for metabolite data to deepen our understanding of factors that influence an individual's response to morphine.

Adverse event reporting in randomised controlled trials of neuropathic pain: considerations for future practice.

High-quality information on the potential benefit and harm of a drug is required for patients and clinicians to make informed treatment decisions and to enable cost-effectiveness modeling to be undertaken. This systematic review describes the collection and reporting of adverse event data as presented in published clinical trials of neuropathic pain for the evaluation of antidepressant or antiepileptic drugs. A total of 74 studies in 16,323 patients published between 1965 and 2012 were identified, of which 43 were published from 2004 onwards. The review found that methods used to collect adverse event data, the frequency of collection, and the selection criteria used by authors for reporting adverse events vary substantially, and these events are often inadequately reported. Consequently, a potential synthesis of valuable harm information across trials is hampered. We make recommendations regarding the reporting of methods used to collect, assess, select, and present adverse event data in publications. Through the Core Outcome Measures in Effectiveness Trials (COMET) initiative, core outcome sets (which include effectiveness and harm) are developed by disease condition. To facilitate data synthesis for adverse events of drug therapies, we suggest that core outcome sets for harms could be developed by therapeutic class (ie, individualized for each class of drug). To improve comparability of information across trials collection methods need to be standardized for patient reports (spontaneous or prompted) and active surveillance (clinical examinations and laboratory tests). Uniform methods for presenting summary information regarding recurrent events, duration and timing of events requires further research.

Analgesia and central side-effects: two separate dimensions of morphine response.

AIMS: To present a statistical model for defining interindividual variation in response to morphine and to use this model in a preliminary hypothesis-generating multivariate genetic association study. METHODS: Two hundred and sixty-four cancer patients taking oral morphine were included in a prospective observational study. Pain and morphine side-effect scores were examined using principal components analysis. The resulting principal components were used in an exploratory genetic association study of single nucleotide polymorphisms across the genes coding for the three opioid receptors, OPRM1, OPRK1 and OPRD1. Associations in multivariate models, including potential clinical confounders, were explored. RESULTS: Two principal components corresponding to residual pain and central side-effects were identified. These components accounted for 42 and 18% of the variability in morphine response, respectively, were independent of each other and only mildly correlated. The genetic and clinical factors associated with these components were markedly different. Multivariate regression modelling, including clinical and genetic factors, accounted for only 12% of variability in residual pain on morphine and 3% of variability in central side-effects. CONCLUSIONS: Although replication is required, this data-driven analysis suggests that pain and central side-effects on morphine may be two separate dimensions of morphine response. Larger study samples are necessary to investigate potential genetic and clinical associations comprehensively.

Interventions to improve symptoms and quality of life of patients with fibrotic interstitial lung disease: a systematic review of the literature.

BACKGROUND: Patients with fibrotic interstitial lung disease have symptom control and quality of life (QoL) needs. This review aims to evaluate the evidence for the use of interventions in improving dyspnoea, other symptoms and QoL. METHODS: Eleven databases, relevant websites and key journals were hand-searched. Studies were assessed and data extracted independently by two researchers using standardised proformas. Meta-analyses were performed where possible with 95% CI. RESULTS: 34 papers with 19 interventions in 3635 patients were included. Meta-analyses showed no significant effect of interferon γ-1b or sildenafil on 6-minute walking distance (6MWD) or dyspnoea. Pulmonary rehabilitation and pirfenidone had a positive effect on 6MWD (mean difference (95% CI) 27.4 (4.1 to 50.7)) and 24.0 (4.3 to 43.7), respectively), and pulmonary rehabilitation had a mixed effect on dyspnoea. Both pulmonary rehabilitation and sildenafil showed a trend towards significance in improving QoL. There was weak evidence for the improvement of 6MWD using oxygen; dyspnoea using prednisolone, diamorphine, D-pencillamine and colchicine; cough using interferon α and thalidomide; anxiety using diamorphine; fatigue using pulmonary rehabilitation; and QoL using thalidomide and doxycycline. A wide range of outcome scales was used and there were no studies with economic evaluation. CONCLUSIONS: There is strong evidence for the use of pulmonary rehabilitation and pirfenidone to improve 6MWD and moderate evidence for the use of sildenafil and pulmonary rehabilitation to improve QoL. Future recommendations for research would include careful consideration of the dichotomy of radical and palliative treatments when deciding on how symptom and QoL outcome measures are used and data presented.

'I wish I knew more ...' the end-of-life planning and information needs for end-stage fibrotic interstitial lung disease: views of patients, carers and health professionals.

The importance at the end of life of developing effective communication and meeting information needs is recognised as being central to enhance patient and family centred experience. This qualitative study aimed to explore understanding of the disease, preferences regarding end-of-life planning, and views on communication and coordination of care in patients with Progressive Idiopathic Fibrotic Interstitial Lung Disease (PIF-ILD). Twelve semistructured in-depth qualitative interviews were conducted among PIF-ILD patients and carers attending two London hospitals. Six Interviews were also conducted among health professionals from one London Hospital, a palliative care service and primary care. There was good understanding of the terminal nature of the disease among both patients and carers, but a poor understanding of prognosis, and how the disease would manifest at the end stages. Both patients and carers expressed a wish to receive more information from clinicians. Health professionals recognised the difficulty of balancing information needs with maintaining hope. No participants were aware of any palliative care input, and no participants had considered important end-of-life issues, such as preferred place of care and preferred place of death. Our work shows that palliative interventions need to be developed for this group of patients which should aim to improve communication and coordination of care, while facilitating discussions surrounding information needs and important end-of-life preferences.

Specialist palliative care is more than drugs: a retrospective study of ILD patients.

BACKGROUND: This study aimed to assess the palliative care needs of progressive idiopathic fibrotic interstitial lung disease (PIF-ILD) populations in two London ILD centres. METHODS: Patients' records from Royal Brompton Hospital (RBH) and King's College Hospital (KCH) were extracted to assess palliative care needs, use of palliative treatments, and whether end-of-life preferences were documented and achieved. RESULTS: Forty-five PIF-ILD patients were identified (26 RBH, 19 KCH). Patients at RBH were younger (37-81 years, median = 61 years) and predominantly white British (23/26) compared to KCH's older, more racially diverse population (70-99 years, median = 82 years, 6/19 nonwhite). Seventeen of 45 patients had specialist palliative care team involvement. Nearly all patients (42/45) experienced breathlessness in their last year of life. Additional symptoms included cough, fatigue, depression/anxiety, and chest pain. All patients given opioids (22/45) or benzodiazepines (8/45) had documented benefit. Nonpharmacological treatments were rarely used. Few patients had preferred place of care (8/45) or preferred place of death (6/45) documented. CONCLUSIONS: Despite demographic variation, the patient populations at the two hospitals experienced similar symptoms. There was use of standard pharmacological treatments with symptom benefit. Nonpharmacological interventions were seldom used and documentation of preferred place of care and preferred place of death was poor.

Coordinate My Care: a clinical service that coordinates care, giving patients choice and improving quality of life.

INTRODUCTION: If palliative care is to lead the way towards a new model for integrated care, the ability to share information across the whole of health and social care is essential. Coordinate My Care (CMC) is a service dedicated to preserving dignity and autonomy at the end of life. Its care pathways enable health professionals from primary and secondary care to put the patient at the centre of health care delivery. This service is underpinned by an electronic solution. The CMC record can be accessed 24/7 by all health and social care professionals who have a legitimate relationship with the patient. PATIENTS AND METHODS: The record displays diagnosis, prognosis, advanced care plan, resuscitation status and patients wishes for end of life care patients across London. This article is a review of CMC use and outcomes from August 2010- March 2012. RESULTS: 1087 CMC patient records were analysed. The primary diagnosis was non-cancer in 52.3%, cancer in 46.3% and unknown in 1.4%, 42% of all patients were cared for by generalist only and had no specialist palliative care involvement. At the time of analysis 207 had died. Actual place of death was home 38.6%, care/nursing home 16.4%, hospice 12.1% and 30% in hospital. This equates to 55% of patients dying in their usual place of residence and reflects that 70% died outside of hospital. CONCLUSION: The CMC service has a well defined pathway underpinned by an electronic solution. It has been shown to change culture and deliver fully integrated, personalised end of life care. A pan-London CMC roll out will take place over the next 12 months.

Symptom burden, survival and palliative care in advanced soft tissue sarcoma.

Introduction. The symptom burden and role of palliative care (PC) in patients with advanced soft tissue sarcoma (STS) are not well defined. Methods. This study retrospectively reviewed both symptoms and PC involvement in patients known to an STS referral centre who died in one calendar year. Results. 81 patients met inclusion criteria of which 27% had locally advanced disease and 73% metastases at initial referral. The median number of symptoms was slowly progressive ranging from 2 (range 0-5) before first-line chemotherapy (n = 50) to 3 (range 1-6) at the time of best supportive care (BSC) decision (n = 48). Pain and dyspnoea were the commonest symptoms. Median overall survival from BSC decision was 3.4 weeks. 88% had PC involvement (either hospital, community, or both) with median time from first PC referral to death of 16 (range 0-110) weeks. Conclusions. Patients with metastatic STS have a significant symptom burden which justifies early PC referral. Pain, including neuropathic pain, is a significant problem. Dyspnoea is common, progressive and appears to be undertreated. Time from BSC decision to death is short, and prospective studies are required to determine whether this is due to overtreatment or very rapid terminal disease progression.

Genetic variation in the catechol-O-methyltransferase (COMT) gene and morphine requirements in cancer patients with pain.

BACKGROUND: Genetic variation contributes to differences in pain sensitivity and response to different analgesics. Catecholamines are involved in the modulation of pain and are partly metabolized by the catechol-O-methyltransferase (COMT) enzyme. Genetic variability in the COMT gene may therefore contribute to differences in pain sensitivity and response to analgesics. It is shown that a polymorphism in the COMT gene, Rs4680 (Val158Met), influence pain sensitivity in human experimental pain and the efficacy for morphine in cancer pain treatment. In this study we wanted to investigate if variability in other regions in the COMT gene also contributes to interindividual variability in morphine efficacy. RESULTS: We genotyped 11 single nucleotide polymorphisms (SNPs) throughout the COMT gene, and constructed haplotypes from these 11 SNPs, which were in Hardy-Weinberg equilibrium. We compared both genotypes and haplotypes against pharmacological, demographical and patient symptoms measurements in a Caucasian cancer patient cohort (n = 197) receiving oral morphine treatment for cancer pain. There were two frequent haplotypes (34.5% and 17.8%) in our cohort. Multivariate analyses showed that patients carrying the most frequent haplotype (34.5%) needed lower morphine doses than patients not carrying the haplotype, with a reduction factor of 0.71 (p = 0.005). On the allele level, carriers of alleles for six of the SNPs show weak associations in respect to morphine dose and the alleles associated with the lowest morphine doses constitute part of the most frequent haplotype. CONCLUSION: This study suggests that genetic variability in the COMT gene influence the efficacy of morphine in cancer patients with pain, and that increased understanding of this variability is reached by expanding from analyses of single SNPs to haplotype construction and analyses.